BONE METASTESES Flashcards
Bone Metastases
Pathophysiology
Biochemical Markers
Adult bones undergo continuous bone remodeling by osteoclasts and osteoblasts. Osteoclasts first break down bone to form a resorption cavity, then this resorption stimulates osteoblasts to form new bone over the resorption cavity
BONE RESORPTION
- urinary calcium
- acid phosphatase
- hydroxyproline
- n-telopeptide
- c-telopeptide
BONE FORMATION
- Bone-specific isoform of alkaline phosphatase
- procollagen peptide fragments (investigational)
Bone Metastases
Management
Summary
Patients with evidence of bone metastases should be treated with Bone modifying Agent with concurrent anticancer treatment
One BMA is not recommended over another
- Pamidronate 90mg IV over at least 2 hours q3-4 weeks
- Zoledronic Acid 4mg IV over at least 15 mintues Q12 weeks or Q3-4weeks
- Denosumab 120mg SQ Q4 weeks
Continue BMA until evidence of substantial decline in pts performance status
Bone Metastases
Management
Bisphosphonates
Inhibits osteoclast maturation and function – pamidronate and ZA approved for this indication in U.S; others being investigated (e.g., clodronate, ibandronate)
Affinity for bone with exposed minerals (areas of osteolysis)
Non-inferiority of q4wk vs. Q12wk
Bone Metastases
Management
Bisphosphonates
SAFETY CONSIDERATIONS
RENAL DYSFUNCTION
Renal Dysfunction
- Dose reductions based on CrCl
- Lengthen the duration of the infusion
Generally do not dose reduce when treating hypercalcemia of malignancy
MONITOR
- SCR
- Electrolytes, Ca, phos, Mag, Hg/HCT
Bone Metastases
Management
Bisphosphonates
SAFETY CONSIDERATIONS
HYPO - CALCEMIA, PHOSPHATEMIA, MAGNESEMIA
Guidelines for zoledronic acid (product information) indicate calcium supplementation should be given to all patients (500mg + 400 IU vitamin D daily)
Do not supplement in a patient with a history of hypercalcemia or extensive bone metastases
Bone Metastases
Management
Bisphosphonates
SAFETY CONSIDERATIONS
Myalgias/Arthralgias
Usually occur w/i 48hrs of first and second dose
Typically managed with NSAID or APAP
Bone Metastases
Management
Bisphosphonates
SAFETY CONSIDERATIONS
Osteonecrosis of Jaw
Usually present as painful, soft tissue swelling and infection
RISK FACTORS
- Chemotherapy, steroids, Advanced BRCA, Multiple Myeloma, periodontal disease
Bone Metastases
Management
Denosumab (Xgeva)
FDA approved to prevent SREs in patients with bone metastases from solid tumors and multiple myeloma at a dose of 120mg SQ every 28 days
Can cause sever hypocalcemia - correct preexisting hypoCA prior to treatment
Also marketed as PROLIA 60mg a6 mo- postmenopausal osteoporosis
Similar risk of ONJ, hypocalcemia, hypophosphatemia of denosumab vs. ZA
Denosumab SUPERIOR to ZA in delaying first on-study SRE
No concerns about Renal Dysfunction
